This invention relates generally to an oral preparation to be used in the prevention and treatment of chronic renal insufficiencies as well as other diseases related to protein metabolism disorders, more specifically to an oral product containing a protein hydrolysate rich in essential amino acids, optimum carbohydrate to protein ratio, and reduced salts, phosphates, and heavy metal content.
It is known that a person with chronic renal insufficiency, kidney disease or damage, or other similar disorders suffer from the effects of the build up of toxic chemicals in the blood, such as ammonia, increased levels of urea, creatinine and other toxic products and metabolites. The level of the concentration of the toxic products varies according to the degree of renal failure. Patient's suffering from chronic renal insufficiency may also suffer from disorders of protein synthesis, anemia, hemopoeisis, hyperlipoproteinemia, disorders of the acid--alkaline and ionic balance and other metabolic disorders.
Generally, the treatment of end stage forms of chronic renal insufficiency is hemodialysis, which is expensive, has side effects, including both physical side effects as well as psycological side effects. In some cases, due to presence of cardiac problems or cardiac decompensation, anemia, or other blood disorders, hemodialysis is inappropriate. All patients suffering from renal disorders, including those who are not good candidates for hemodialysis, would greatly benefit from prophylaxis and treatment with oral therapy to relieve or reverse the symptoms of chronic renal insufficiency, including hyperazotemia and other metabolic disorders.
In the traditional prophylactic oral treatment of nitrogen retention and hyperazotemia in patients with chronic renal insufficiency special attention is usually paid to diet and nutritional therapy. One goal is to reduce the overall oral intake of nitrogen containing compounds such as proteins and toxic non-protein nitrogen containing compounds. Another goal of diet therapy in patients with chronic renal insufficiency was to stimulate the metabolic turnover process in which the ammonia by-products in the blood are reused in the creation of amino acids, purines and other biologically important nitrogen containing compounds so as to reduce the circulating levels of ammonia. Other objects of nutritional therapy are to normalize the electrolyte values, reduce hyperlipidemia, correct hyperphosphatemia, and to reduce the filtration load on the kidneys.
The disadvantages of the known oral therapies for the prophylaxis and treatment of chronic renal insufficiency and hyperazotemia are well known. For example, oral essential amino acids supplements and foods such Amin-Aid (American McGaw), and Travasorb Renal Powder (Travenol Laboratories) are expensive, and have high osmolalities. Treatment can result in osmotic diarrhea, which can exacerbate electrolyte problems.
Essential amino acid products are also provided for intravenous infusion, for example Nephramine (American McGaw) or Renamin (Travenol Laboratories). These products, however, are also very expensive and require intravenous administration. The essential amino acids products are mixed with high density dextrose solution to obtain an appropriate calorie to nitrogen ratio. The solutions are generally introduced through a central venous catheter. The risks associated with central venous administration of amino acid solutions, such as emboli, infection, fluid overload, etc., are well documented.
Recently, oral forms of deaminated aminoacids (alpha-ketoacids), such as ketosteril (Fresenius, Republic of Germany), have been used for controlling circulating ammonia in patients with renal failure. The alpha-ketoacids function by utilizating circulating nitrogen to create proteins. However alpha-ketoacid products are very expensive, not readily accessible, and do not provide a ready source of energy.
Besides treating patients suffering from chronic renal insufficiency with essential amino acids or alpha-ketoacids, other traditional therapy is used. For example, some patients are treated with diuretics to increase the excretion of toxic products. Diuretics, however, affect the electrolyte balance, increase blood viscosity and increase filtration load on insufficient nephrons. Moreover, systematic treatment with diuretics can result in other problems such as an overloading of the liver and other organs.
Preparations from natural sources have been used to stimulate the function of the nephrons. For example, lespecapitosides (lespenephril, Natermann, Spain) is used to treat uremia. This product has an uncertain effect on the kidney and often has cardiac and circulatory side effects. Moreover, this product does not provide the necessary regenerative building blocks and energy source to positively effect the kidney. Canrenoate potassium (Kanrenol, Boots, Italy) is also used to treat hyperaldosteronism and is used in patients with chronic renal insufficiency. Kanrenol suffers from many of the same draw backs as lespenephril.
Finally, diet foods, with undefined or crude protein constituants, have been used. The crude proteins are often insoluble in water and difficult to accurately incorporate into oral formulas. Moreover, there is uncertain utilization of the amino acids in such proteins by a patient suffering from chronic renal insufficiency. The undefined protein constituents are not readily utilizable and not sufficiently effective due to their poor digestion. The crude proteins contain salts and heavy metals.
As stated above, inappropriate or excessive administration of protein can result in hyperazotemia. Many prior art nutritional preparations, both oral or intravenous are comprised of both essential and non-essential amino acids. The use of currently available amino acids products can result in azotemia. Furthermore, some products are not appropriate for use by patients with chronic renal insufficiency due to the presence of hazardous levels of salts such as sodium chloride, sodium and potassium phosphates, and sulfates. For example, an oral protein hydrolysate briefly available, was Algomed (Nectacorp, Bulgaria). Algomed was an experimental product that proved unsatisfactory because of the high salt content, particularly high sodium phosphate level. Stark protein (Cernelle, Switzerland) is an oral protein supplement used by athletes.
Furthermore, oral or food products used in patients with chronic renal insufficiency use protein sources which are not sufficiently water soluble and thereby difficult to prepare a proper dose for a critically ill patients who can be maintained on oral therapy.